TERRAFORMING TERRA
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Saturday, July 6, 2013

Comparing DNA on Extreme Phenotype s Fruitful

This
is an enhanced statistical approach able to detect anomalies that are
worth pursuing. It is a case of avoiding simple controls for
extremes and rather obviously we can in fact establish several such
extremes to act as a set to use against the test material. This
promises to flush out good data that may well be important but
otherwise well under the radar.

We
are certainly still learning to interpret DNA and to manipulate it
effectively, in spite of our occasional rush to market scenarios.

All
this continues to inform a rapidly emerging technology that will
ultimately can be expected to resolve all human health issues.

Comparing centenarians to extremely sick diabetic people has
found more genes that cause diabetes

Aging researcher
compared centenarians on one side and T2D patients with severe
complications (people with extreme diabetic complications) on the
other, thus maximizing possible genetic differences among patients
and controls. Their data suggest that the use of relatively small
numbers of cases and controls with extreme phenotypes (thus reducing
sample heterogeneity) in genetic association studies of age-related
diseases can be successful in detecting significant associations.

This method
might be used for intelligence related genes by comparing genius
IQ people with people with far below normal intelligence instead
of against average intelligence people as the control group.

Genetic
association studies of age-related, chronic human diseases often
suffer from a lack of power to detect modest effects. Here an
alternative approach of including healthy centenarians as a more
homogeneous and extreme control group. As a proof of principle they
focused on type 2 diabetes (T2D) and assessed /genotypic associations
of 31 SNPs associated with T2D, diabetes complications and metabolic
diseases and SNPs of genes relevant for telomere stability and
age-related diseases. They hypothesized that the frequencies of risk
variants are inversely correlated with decreasing health and
longevity. They performed association analyses comparing diabetic
patients and non-diabetic controls followed by association analyses
with extreme phenotypic groups (T2D patients with complications and
centenarians).

Results drew
attention to rs7903146 (TCF7L2 gene) that showed a constant increase
in the frequencies of risk genotype (TT) from centenarians to
diabetic patients who developed macro-complications and the strongest
genotypic association was detected when diabetic patients were
compared to centenarians (p_value = 9.066*10^-7). They conclude
that robust and biologically relevant associations can be obtained
when extreme phenotypes, even with a small sample size, are compared.

Using
this methodological approach on a total of 1,349 individuals we
tested 31 SNPs in or nearby 16 different genes that were previously
strongly associated with T2D and metabolic diseases and that could be
considered good candidate to play a role in T2D complications, on the
basis of other large genetic studies.

Our results
indicate that most of the SNPs analyzed were not significantly
associated with T2D, even when extreme groups of cases and controls
were used. This somewhat unexpected result could be due to a lack of
biological relevance in spite of their previously strong association
signal in GWASs. Indeed, a major drawback of GWASs is the observation
of many significant association signals from loci of weak effect.
Therefore, we have to consider the possibility that such SNPs,
despite having reached statistical significance in large GWASs, could
have a weak biological relevance. Indeed, the presence of risk
alleles at the same frequency in T2D patients with or without
complications and in centenarians suggests that per se they do not
represent a strong biological risk, being compatible with exceptional
longevity, and that they likely necessitate to interact (epistatic
effects) with (many) other risk alleles and/or specific environmental
conditions to give a certain phenotype. Further studies, possibly in
more than one population, are needed to test this possibility.

The two SNPs
that reached statistical significance in our study were ADIPOQ
rs266729 and TCF7L2 rs7903146, the last one being the strongest.
ADIPOQ encodes for adiponectin, the most abundant adipokine in human
plasma. Low adiponectin levels are associated to IR and T2D and the
chromosome locus 3q27, where ADIPOQ is located, is linked to
metabolic syndrome and T2D. Several studies have investigated the
association between ADIPOQ polymorphisms and T2D, but their results
are controversial, probably due to differences in the size and in the
composition of the analyzed cohorts. To this regard it is
interesting to note that the statistical significance of ADIPOQ
rs266729, a polymorphism associated to decreased adiponectin levels,
emerged only when T2D patients were compared with centenarians.

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About Me

Apr 2017 - 4.1 Mil Pg Views, March 2013 - Posted my paper introducing CLOUD COSMOLOGY & NEUTRAL NEUTRINO rigorously described as the SPACE TIME PENDULUM, September 2010 I am pleased to report that my essay titled A NEW METRIC WITH APPLICATIONS TO PHYSICS AND SOLVING CERTAIN HIGHER ORDERED DIFFERENTIAL EQUATIONS' has been published in Physics Essays(AIP) and appeared in their June 2010 quarterly. 40 years ago I took an honors degree in applied mathematics from the University of Waterloo. My interest was Relativity and my last year there saw me complete a 900 level course under Hanno Rund on his work in relativity,as well as differential geometry(pure math) and of course analysis. I continued researching new ideas and knowledge since that time and I have prepared a book for publication titled Paradigms Shift&. I maintain my blog as a day book and research tool to retain data and record impressions and interpretations on material read. Do join my blog and receive Four items of interest daily Monday through Saturday.